The longer I continue in practice, the more complex it becomes. I thought advances in our understanding of the molecular basis of cancer would clarify decision making ; instead answers have led to more questions. In the spirit of the immortal Henny Youngman: Take the issue of cancer screening, please.
The story of screening for colorectal cancer (CRC) and prostate cancer has many similarities. The primary screening and diagnostic tool during my training years was the digital rectal exam (DRE). In CRC the manual examination was (and still is) supplemented with stool occult blood testing. A positive result usually leads to an invasive procedure, e.g., barium enema or colonoscopy. Not fun procedures. And if the test is falsely positive, not only is unnecessary time wasted, cost expended, and anxiety generated, but severe morbidity (bowel perforation) and possible mortality can result.
Enter the great hope: the carcinoembryonic antigen (CEA). Finally a simple blood test that would solve all our problems. It was originally marketed as a specific screening test that should save lives. But within a short period of time, it was discovered that a positive test wasn’t specific for CRC and a negative test did not always rule it out. CEA determinations are still useful in following patients treated for CRC to get an idea if they are responding or not. But, they are not reliable enough in diagnosing CRC let alone reducing mortality from the disease. Thus, CEA testing is not recommended as a screening test for the general population.
Contrary to the experience with CEA, PSA (prostate specific antigen) screening for prostate cancer has been made available to all middle age and elderly men for 20 years. Its utility has not been seriously questioned until the U.S. Preventive Services Task Force (USPSTF) reviewed two negative clinical trials and recommended that PSA not be used to screen the population at large. As with changes in recommendations involving screening mammograms made by USPSTF two years previously, response and pushback has been vocal and immediate. But, these two trials demonstrated that PSA-based screening of the general population does not save lives.
I found the article “Prostate-Cancer Screening — What the U.S. Preventive Services Task Force Left Out” in the New England Journal of Medicine frames the debate about screening into its proper perspective. They point out that PSA is not a cancer-specific protein and there is a wide variation in aggressiveness across the spectrum of prostate cancer. Therefore, “controversy and debate about PSA screening were predictable from the outset.” They cite three issues the panel didn’t address even though they “agree fully with the task force’s analysis”:
- Every guideline recommends discussing the benefit/risk ratio and individualizing screening decisions taking into account patient values and preferences. In this era of consumerism, a laudable approach. However, before the publication of the two trials mentioned above, no data existed to support screening. So a discussion based on evidence was impossible. “Thus, patients were not really making informed decisions, and office-based discussion of the pros and cons of PSA testing was essentially a charade. Instead, most patients’ decisions reflected their general concerns about cancer or their general inclination to accept (or resist) medical interventions”.
I lost count of the number of times lengthy discussions ended with patient and family saying that I was the doctor and should make decisions for them. Even in this age of patient advocacy. As the NEJM article points out, the two screening trials only add to the confusion in that one did not demonstrate any mortality benefit while the other demonstrated a small reduction in prostate cancer related mortality, and there were differences in methodology between them.
- Management of individual and serial PSA values is inconsistent and unpredictable even within practices. Physicians are trying to adopt reproducible practices, but “the guidelines are vague precisely because the limitations of PSA screening preclude the kind of rational, standardized, evidence-based algorithm that should inform any routine preventive intervention”. When one of my colleagues nonchalantly proclaims to practice Evidence-Based Medicine, I remain skeptical.
- It has been estimated that $5.2 million is spent screening everyone to prevent one death from prostate cancer. This does not include excessive PSA testing and extra encounters. So some estimate the actual cost to be more than double this figure. The authors argue that there are other more pressing uses for this money. The argument that Black men, who have a higher incidence of prostate cancer than whites, should be screened. Statistics don’t bear this out since the proportion of deaths from prostate cancer in 2007 was 3.3% in blacks and 2.3% in whites. The difference is not great enough to justify race related screening, even if we knew how to do it.
A New York Times article entitled, Considering When It Might Be Best Not to Know About Cancer, raises the possibility that more screening may not be productive and could possibly be harmful. In 2009, the USPSTF, charged with reviewing evidence and publishing screening guidelines, recommended that screening mammograms not be performed on women in their 40’s, and they be reduced to every other year up to age 74. A similar backlash occurred.
Richard Just is an oncologist who blogs at @JustOncology.
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